A myofibroblast is a specialized cell that combines features of a fibroblast and a smooth muscle cell. These cells primarily participate in tissue remodeling and repair. To identify and study these cells, scientists rely on biological markers, which are specific molecules that signal the presence of a particular cell type. Because myofibroblasts are most active during processes like wound healing, these markers are important tools for researchers to track their location and activity.
The Function of Myofibroblasts
Myofibroblasts are central to the body’s healing process after an injury. When tissue is damaged, these cells are recruited to the site to mend the wound. A primary function is their ability to contract, physically pulling the edges of a wound closer together. This is achieved through an internal system of fibers. They also produce and deposit new extracellular matrix, a scaffold-like substance rich in collagen that provides structure to the repairing tissue, eventually forming a scar.
This beneficial function can become detrimental when the process is unregulated. In chronic diseases, the persistent activity of myofibroblasts leads to fibrosis, the excessive scarring of an organ. This condition can impair the function of organs such as the lungs, liver, and kidneys. In cancer, myofibroblasts can create a supportive environment, known as the stroma, that nurtures tumor growth, highlighting their dual role in healing and disease.
Common Myofibroblast Markers
To identify myofibroblasts, scientists look for specific proteins characteristic of this cell type. The most widely recognized marker is alpha-smooth muscle actin (α-SMA). This protein is a component of the cell’s contractile machinery, forming stress fibers that grant the myofibroblast its ability to contract tissues. Expression of α-SMA is a defining feature of a fully differentiated myofibroblast.
Another frequently used marker is vimentin, an intermediate filament protein that forms part of the cell’s cytoskeleton. While vimentin is found in myofibroblasts, it is not exclusive to them, as it is also present in many other mesenchymal cells. For this reason, it is not used as a standalone identifier.
A more specific marker used in disease research is Fibroblast Activation Protein (FAP), a serine protease found on the cell’s surface. Its expression is more restricted than α-SMA or vimentin and is strongly associated with myofibroblasts in fibrotic tissues and the stroma surrounding tumors. This specificity makes FAP a subject of interest for targeted therapies in cancer and fibrotic diseases.
The materials myofibroblasts produce and secrete can also act as indirect indicators of their activity. These cells produce extracellular matrix components, and the presence of large amounts of type I and type III collagen or fibronectin often signals a myofibroblast population. A splice variant of fibronectin, known as EDA-FN, is a marker of matrix synthesis in fibrotic conditions.
Marker Expression in Different Tissues
The identification of myofibroblasts is complicated because their protein expression can vary significantly depending on the tissue and biological context. For instance, a myofibroblast in the liver during fibrosis may express a different combination of markers than one found in a healing skin wound. This variability means that no single marker is sufficient for identification.
To address this complexity, scientists employ a panel of multiple markers to identify myofibroblasts with greater confidence. Staining a tissue sample for several different proteins simultaneously, such as α-SMA and FAP, helps distinguish myofibroblasts from other similar cell types. This multi-marker approach provides a more complete understanding of their function within a specific tissue environment.
Techniques for Marker Detection
Scientists use laboratory techniques to visualize protein markers that identify myofibroblasts within tissue samples. One of the most common methods is immunohistochemistry (IHC). This technique uses antibodies engineered to bind to a specific target protein. These antibodies are linked to an enzyme that produces a colored precipitate when a chemical substrate is added, allowing researchers to see the location of the marked cells under a light microscope.
Another visualization method is immunofluorescence (IF). Similar to IHC, this technique uses antibodies to target specific markers, but they are linked to fluorescent molecules called fluorophores instead of an enzyme. When illuminated with light under a fluorescence microscope, the fluorophores emit colored light, causing the marked cells to glow. This method allows for visualizing multiple markers at once by using different colored fluorophores for each antibody.